美国一项新研究显示，老年人的人体昼夜节律（又称生物钟）较弱或不规律，可能会增加罹患痴呆症的 风险。相关论文发表在美国《神经学》期刊上。 昼夜节律是生物体内在的24小时活动规律，调控体温、睡眠、心率、代谢、激素分泌等生理过程，使身 体活动与自然环境（主要是光线明暗变化）同步。昼夜节律紊乱会导致多种健康问题，并可能是痴呆症 等神经退行性疾病的风险因素。 （来源：沈阳日报） 转自：沈阳日报 为了观察昼夜节律与老年人患痴呆症风险的关联，美国得克萨斯大学达拉斯西南医学中心等机构的研究 人员进行了一项调查，涉及2183名平均年龄79岁、开始调查时未患痴呆症的人。 参与者平均佩戴12天监测设备，记录心脏活动的变化，以衡量身体昼夜节律的强度和规律性。按照昼夜 节律的相对振幅，参与者被分为高、中、低三组。相对振幅较高表示活跃阶段与静息阶段的差异较大， 身体昼夜节律较强。 研究人员随后对参与者进行平均3年的随访，这期间有176人被诊断患上痴呆症，约占总人数的8%。高 振幅组的728人中有31人患上痴呆症，而低振幅组的727人中有106人患上痴呆症。研究显示，综合考虑 年龄、血压、心脏病等因素后，低振幅组患痴呆症的风险达到高振幅组 ...

Core Viewpoint - GLP-1 class drugs, including semaglutide and tirzepatide, show potential in treating not only type 2 diabetes and obesity but also various neurological and psychiatric disorders, supported by emerging clinical data [1][2][6]. Group 1: Mechanism and Applications - GLP-1 drugs activate GLP-1 receptors to enhance insulin secretion, suppress glucagon secretion, slow gastric emptying, and reduce appetite, leading to weight loss [1]. - These drugs have been approved for treating type 2 diabetes, obesity, cardiovascular diseases, kidney diseases, and metabolic liver diseases [1]. - Recent studies indicate that GLP-1 drugs may have therapeutic benefits for neurodegenerative diseases, substance use disorders, and other neurological conditions [2][3][6]. Group 2: Clinical Evidence and Safety - A review of clinical evidence highlights the potential of GLP-1 drugs in treating Parkinson's disease and Alzheimer's disease, with a focus on their neuroprotective properties [6][7]. - There is increasing evidence that GLP-1 drugs may reduce addictive behaviors in individuals with substance use disorders [6]. - Most patients with neuropsychiatric disorders using GLP-1 drugs have shown acceptable safety profiles, although large-scale confirmatory trials are still lacking [6][13]. Group 3: Future Research Directions - The role of GLP-1 drugs in neurological conditions will continue to evolve as new clinical trial data emerges, providing clearer evidence of their potential uses and limitations [13]. - Despite enthusiasm for GLP-1 drugs in treating central nervous system diseases, no large-scale trials have yet confirmed their efficacy and safety in these areas [13].

Core Viewpoint - The article discusses the increasing interest and cautious use of GLP-1 medications for weight management in the elderly population, highlighting both potential benefits and necessary precautions in their application [4][8][12]. Group 1: GLP-1 Medications in Elderly Care - GLP-1 medications have gained popularity among patients aged 65 and older, with many seeking these treatments for obesity management [4]. - The CDC reports that nearly 40% of individuals aged 60 and above are classified as obese, which significantly impacts their health and quality of life [5]. - Experts emphasize the need for careful evaluation of elderly patients before prescribing GLP-1 medications, particularly for those with frailty or cognitive impairments [8][12]. Group 2: Broader Implications of GLP-1 Medications - Recent studies suggest that GLP-1 medications may have effects beyond glucose control and weight loss, potentially influencing cardiovascular health, addiction behaviors, certain cancers, and cognitive function [6][11]. - In the context of neurodegenerative diseases, GLP-1 medications may help slow cognitive decline due to their anti-inflammatory properties and ability to improve insulin signaling [11]. - Research indicates that patients using GLP-1 receptor agonists have lower all-cause mortality rates compared to those on other diabetes treatments, although the relationship with different cancer types remains unclear [11]. Group 3: Clinical Considerations and Future Research - The complexity of medication decisions for elderly patients necessitates a comprehensive assessment of their overall health, including potential side effects and interactions with other medications [12]. - Experts advocate for a gradual approach to GLP-1 treatment, focusing on maintaining strength, independence, and quality of life rather than solely on weight loss [12]. - There is a recognized need for more representative clinical trial data for older populations, as current studies show that older patients may experience higher rates of discontinuation due to gastrointestinal side effects [12].

来源：人民日报海外版 克利夫兰参加论坛。世界顶尖科学家论坛供 图 渐冻症，学名肌萎缩侧索硬化，英文缩写ALS。 肌肉逐渐萎缩、无力，慢慢地，从健步如飞到无法张嘴说话，直至瘫痪，似乎身体被逐渐冻住……十多 年前那场网络"冰桶挑战"，让很多人意识到，世界上竟然还有如此可怕的疾病，几乎与"绝症"画上等 号。 唐·克利夫兰，是那个正一点点擦掉这个"等号"的人。这位美国神经生物学家与肿瘤学家，凭借对遗传 性渐冻症的发病机制研究，以及探索渐冻症等疾病的新疗法等成就，获得2018年"生命科学突破奖"。该 奖由数位跨国互联网企业家设立，有"科学界的奥斯卡奖"之誉。 2025世界顶尖科学家论坛开幕前一天，大江东-复旦融媒体创新工作室成员在上海临港中心见到了这位 给渐冻症患者带来希望的科学家。 谈及科研之路上的关键词，克利夫兰给出了颇为"老派"的答案——"生物学和医学领域，聪明固然是好 事，但它既不是成功的必要条件，也不是充分条件；擅长做实验也很好，但同样既非必要也非充分条 件。成功唯一必需的特质，是毅力。" 大家公认的"事实"可能并非事实 渐冻症是一种神经退行性疾病，帕金森病、阿尔茨海默病、亨廷顿舞蹈症都属于此类，或是身体不受 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 迈纳特基底核 （ nucleus basalis of Meynert，nbM） ，作为基底前脑的主要胆碱能输出核团，具有调控皮层功能、学习与记忆等重要作用。 nbM-皮层胆碱能 通路 的功能失调与 神经退行性疾病 （例如 阿尔茨海默病 ） 及 神经发育障碍 （例如 唐氏综合征 ） 密切相关。 2025 年 12 月 4 日， 南京医科大学药学院 刘妍 教授、 南京医科大学 基础医学院 郭兴 教授、 南京医科大学 附属妇产医院 程青 教授及华东师范大学 董毅 教 授作为共同通讯作者 （王达、张馨月、唐晓艳、甘义霞、余汉文为共同第一作者） ，在 Cell Stem Cell 上发表了题为： Generation of human nucleus basalis organoids with functional nbM-cortical cholinergic projections in transplanted assembloids 的研究论文。 该研究构建了 人源基底核类器官 ，并在其移植类器官组装体中形成了具有 功能性的基底核–皮层胆碱能投射，其在研究 nbM ...

编辑丨王多鱼 排版丨水成文 撰文丨王聪 多细胞生物在发育过程中，存在着多种预定的、受到精确控制的细胞程序性死亡，例如细胞凋亡 （Apoptosis） 、 程序性坏死 （Necroptosis） 、 细胞焦亡 （Pyroptosis） ，以及铁死亡 （Ferroptosis） 等。 其中， 铁死亡 （Ferroptosis） 是于 2012 年发现的一种铁依赖性的新型细胞程序性死亡方式，由过度堆积的过氧化脂质 诱导发生，其形态特征，作用方式以及 分子机制与其他程序性死亡方式截然不同。 与此同时，细胞中也有多个对抗铁死亡的途径 （尤其是癌细胞） ——例如 GPX4 所介导的通过谷胱甘肽 （GSH） 特异性催化过氧化脂质来抑制铁死亡。 实际上，在 "铁死亡"这一术语被提出之前，德国 亥姆霍兹慕尼黑研究中心 Marcus Conrad 教授团队就已揭示了 GPX4 通过阻止细胞和小鼠中无限制的磷脂过氧 化，调控一种新的非凋亡细胞死亡类型。 2025 年 12 月 4 日， Marcus Conrad 教授团队在国际顶尖学术期刊 Cell 发表了题为： A fin-loop-like structure in GPX4 ...

Core Insights - A recent study published in *Nature* indicates that young athletes suffering repeated brain impacts may experience neuronal loss long before signs of neurodegenerative diseases appear [1][2] - Chronic Traumatic Encephalopathy (CTE), associated with repetitive brain impacts, is primarily diagnosed post-mortem through the detection of abnormal tau protein accumulation [1] - The study analyzed brain tissue from 28 individuals under 51 years old, revealing that all contact sport athletes exhibited higher levels of neuroinflammation, vascular damage, and neuronal loss compared to non-athlete controls [1] Group 1 - The study found that contact sport athletes had a 56% reduction in cortical layer neurons compared to age-matched individuals without brain injuries, indicating significant early neuronal loss [1] - This neuronal loss occurs independently of tau protein accumulation, suggesting it happens earlier and is not typical of CTE pathology [1] - The findings underscore the need for early identification and treatment of brain injuries in young athletes [2] Group 2 - The research highlights the importance of protecting young athletes and proposes new directions for potential diagnostic and therapeutic targets related to brain changes from repetitive impacts [2]

Summary of the Conference Call on Maiwei Biotech and the Tracer Project Company and Industry Overview - **Company**: Maiwei Biotech - **Industry**: Neurodegenerative Diseases, specifically focusing on Parkinson's Disease (PD) and Multiple System Atrophy (MSA) through the Tracer project [2][4] Key Points and Arguments 1. **Tracer Project Overview**: - Tracer is a novel radiolabeled small molecule drug targeting PD and MSA, with significant application potential and a clear clinical development path [2][4] - It is the only team globally developing such a tracer for PD, aiming to be the first approved tracer for this condition [2][4] 2. **Funding and Support**: - The project has received unconditional funding from the MicroG Fox Foundation, indicating strong scientific and commercial backing [2][5] - Collaboration with top research institutions, including the Chinese Academy of Sciences, enhances the project's credibility and potential [2][6] 3. **Clinical Development Timeline**: - FDA IND approval is expected in 2025, with the first patient enrollment planned for Q4 2025 [5][6] - The Chinese IND is anticipated to be approved in early 2026, with over 100 patient imaging studies already conducted at Huashan Hospital [5][6] 4. **Market Potential**: - The Tracer project targets a large unmet market for PD, with no similar products currently approved, positioning Maiwei Biotech to set new treatment standards [6][10] - The project is expected to solidify Maiwei's position in the chronic disease sector, particularly in age-related diseases [6][10] 5. **Operational Model**: - Maiwei is the largest external investor in the project, which operates independently but leverages Maiwei's core operational capabilities [3][8] - The company plans to explore overseas licensing and transfer opportunities as the project matures [9][20] 6. **Clinical Trial Design**: - Phase I trials will focus on safety, radiation dosimetry, and pharmacokinetics, with a target enrollment of 20 to 30 patients [15][22] - The project faces challenges in obtaining post-mortem data for validation, which may require international collaboration [15][22] 7. **Challenges in Commercialization**: - High costs and lack of insurance coverage for PD diagnostics may hinder market acceptance [15][18] - The company plans to integrate diagnostic tools with therapeutic drugs to enhance market uptake [15][18] 8. **AI Integration**: - AI technology is being explored to improve imaging analysis and diagnostic accuracy, potentially increasing market penetration [16][18] 9. **Future Development Plans**: - Maiwei is committed to expanding its pipeline in neurodegenerative diseases, including Alzheimer's, while adopting differentiated strategies to enhance drug development efficiency [14][24] 10. **Shareholding Structure**: - Maiwei holds a 35% stake in the Tracer project, with plans to potentially increase investment to meet clinical needs and achieve commercialization [23][24] Additional Important Insights - The Tracer project is positioned as a first-in-class solution in the PD space, with significant implications for future investment returns compared to the Alzheimer's market, which has multiple approved tracers [10][12] - The collaboration with international partners and the establishment of a robust BD network are crucial for the project's success and future opportunities [11][19]

Core Insights - The article discusses a significant study from Stanford University published in *Nature*, which reveals that decision-making in the brain is a distributed process rather than being solely controlled by the cortex, suggesting a more complex understanding of brain function and potential new targets for treating neurological diseases [2]. Group 1: Research Findings - The study created a comprehensive map of neural activity in mice during complex behaviors, indicating that brain decision-making involves various regions, including subcortical areas, which can show selection signals earlier than the cortex [2]. - This research challenges the traditional view of the brain as a centralized command center and opens new avenues for understanding and treating neurological disorders [2]. Group 2: Industry Engagement - In conjunction with World Alzheimer's Day, the article prompts reflection on the complexities of neurodegenerative diseases and the potential for better utilization of mouse and cell models in research [5]. - A survey is initiated to gather insights on research pain points and industry trends, offering participants a chance to receive a resource package on neuroscience research and win various prizes [5][7]. Group 3: Product Offerings - The company offers over 20 types of gene-edited and drug-induced mouse models for neurological and muscular diseases, including various knockout and transgenic models tailored to researchers' needs [9]. - Specific mouse models for diseases such as Alzheimer's, Parkinson's, and spinal muscular atrophy are detailed, showcasing the company's commitment to providing relevant research tools [10][11].

Core Insights - Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig's disease, is characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to muscle atrophy and loss of motor function [2][3] - ALS is classified as a neurodegenerative disease, similar to Alzheimer's and Parkinson's, and is currently considered incurable, with treatment focused on stabilizing or delaying the progression of the disease [2][3] Drug Availability - Currently, there are "two and a half" drugs available for ALS treatment: Riluzole from Sanofi, Edaravone from Mitsubishi Pharma, and Tofersen from Biogen, which is effective for only 2% of patients [4] Patient Symptoms and Disease Progression - Early symptoms of ALS may include insomnia, anxiety, and weight loss, with later stages leading to speech difficulties, swallowing issues, and abnormal bowel and bladder function [5][9] - The disease progresses rapidly, with many patients having a life expectancy of around five years post-diagnosis [4] Quality of Life Improvement - Early diagnosis and treatment are crucial, as the average delay in diagnosis has historically been 10-11 months, but awareness is improving, allowing for earlier intervention [6] - Early diagnosis is also vital for new drug development, as clinical trials often require early-stage patients [6] Disease Mechanisms and Triggers - The exact causes of ALS remain unclear, but potential mechanisms include excessive neuronal excitation, insufficient energy metabolism, and oxidative stress [9][10] - Factors such as weight loss, high-altitude exposure, and physical or mental stress can accelerate the onset of ALS symptoms [9][10] Misconceptions and Myths - There is a condition known as "pseudo-ALS" that mimics ALS but has a clear cause and can be treated effectively, with about 5% of suspected ALS cases falling into this category [11] - The placebo effect is a significant concern in ALS treatment, as patients may perceive improvements that are not clinically substantiated [11] Technological Advancements - Brain-computer interfaces could significantly enhance the quality of life for ALS patients by enabling communication and interaction with the outside world, especially in advanced stages of the disease [12]